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This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive participant cohorts with advanced solid tumors will receive pembrolizumab to assess the safety and tolerability of monotherapy. In Parts B, C, and D, participants with advanced non-small cell lung cancer (NSCLC) will receive pembrolizumab in combination with either cisplatin/pemetrexed or carboplatin/pemetrexed (Part B); with either carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Part C); or with ipilimumab (Part D) by non-random assignment to assess the safety and tolerability of the combination therapy. In Part E, participants with untreated Extensive-disease (ED) Small Cell Lung Cancer (SCLC) will receive pembrolizumab in combination with either cisplatin/etoposide, carboplatin/etoposide, or cisplatin/etoposide with prophylactic use of granulocyte colony-stimulating factor (lasting G-CSF [pegfilgrastim]) by non-random assignment to assess the safety and tolerability of the combination therapy.

A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer.

In Part B, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 + IV Pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Cisplatin 75 mg/m^2

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Pemetrexed 500 mg/m^2

Administered as an IV infusion on Day 1 of each 21-day cycle

Experimental: Pembrolizumab+Carboplatin/Pemetrexed

In Part B, participants receive IV Pembrolizumab 200 mg + IV Carboplatin Area Under The Curve (AUC) 5 mg/mL/minute + IV Pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Pemetrexed 500 mg/m^2

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Carboplatin AUC 5 mg/mL/min

Administered as an IV infusion on Day 1 of each 21-day cycle

Experimental: Pembrolizumab+Carboplatin/Paclitaxel

In Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute + IV Paclitaxel 200 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Carboplatin AUC 6 mg/mL/min

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Paclitaxel 200 mg/m^2

Administered as an IV infusion on Day 1 of each 21-day cycle

Experimental: Pembrolizumab+Carboplatin/Nab-paclitaxel

In Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute on Day 1 of each 21-day cycle + IV Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Carboplatin AUC 6 mg/mL/min

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Nab-paclitaxel 100 mg/m^2

Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle

Other Name: ABRAXANE®

Experimental: Pembrolizumab+Ipilimumab

In Part D, participants receive IV Pembrolizumab 200 mg on Day 1 of each 21-day cycle + IV Ipilimumab 1 mg/kg on Day 1 of every other 21-day cycle (every 42 days) for a maximum of 18 cycles of Ipilimumab (35 doses of Pembrolizumab).

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Biological: Ipilimumab 1 mg/kg

Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)

Other Name: YERVOY®

Experimental: Pembrolizumab+Cisplatin/Etoposide

In Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Cisplatin 75 mg/m^2

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Etoposide 100 mg/m^2

Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle

Other Name: TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®

Experimental: Pembrolizumab+Carboplatin/Etoposide

In Part E, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 5 mg/mL/minute on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

Biological: Pembrolizumab 200 mg

Administered as an IV infusion on Day 1 of each 21-day cycle

Other Name: KEYTRUDA®

Drug: Carboplatin AUC 5 mg/mL/min

Administered as an IV infusion on Day 1 of each 21-day cycle

Drug: Etoposide 100 mg/m^2

Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle

Other Name: TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®

Experimental: Pembrolizumab+Cisplatin/Etoposide+G-CSF

In Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles + lasting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) 3.6 mg on Day 4 of Cycle 1. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks for up to 2 years.

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Layout table for eligibility information

Ages Eligible for Study:

20 Years and older (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

In Part A: has a histological or cytological diagnosis of solid tumor, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy

In Part B, C, and D: has a histologically- or cytologically-confirmed diagnosis of NSCLC (Stage IIIB/IV) and are naïve to systemic therapy

In Part C: has a histologically- or cytologically-confirmed diagnosis of squamous cancer

In Part E: has a histologically- or cytologically-confirmed diagnosis of SCLC (ED stage) and are naïve to systemic therapy

Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Has adequate organ function

Female participants of reproductive potential must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)

Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 120 days after the last dose of study therapy and for up to 180 days after the last dose of chemotherapeutic agents

Exclusion criteria:

Has had cancer therapy within 2 weeks (Part E) or 4 weeks (Parts A, B, C, and D) prior to the first dose of study therapy, or not recovered from the adverse events of agents administered more than 4 weeks prior to the first dose of study therapy.

Is currently participating or has participated in a study with an investigational agent or using an investigational device within 30 days of first dose of study therapy

Is expected to require any other form of antineoplastic therapy while on study

Is on chronic systemic steroid therapy within two weeks prior to the first dose of trial treatment or on any other form of immunosuppressive medication

For Part C: Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events version 4 criteria

Has interstitial lung disease detected by chest computed tomography (CT), or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.